Characterization of 12p molecular events outside ETV6 in complex karyotypes of acute myeloid malignancies

Acute myeloid disorders with rearrangements of 12p outside the ETV6 gene we re characterized by fluorescence in situ hybridization (FISH) with a panel of DNA probes. Seven patients with de novo acute myeloid leukaemia (AML), o ne with secondary acute myeloid leukaemia (sAML), and one in the blast phas e of chronic myeloid leukaemia (CML-BP) were enrolled in the study. All AML cases showed multiple karyotypic changes. Chromosome 5 and/or 7 deletions were the most frequent accompanying changes. FISH revealed amplification, c ryptic translocation, and fragmentation of chromosome 12, not discernible a t karyotypic level. Different karyotypic rearrangements of 12p showed a com mon molecular event. Among the seven cases in which breakpoints could be de termined, six were telomeric and one centromeric to ETV6. In three AML case s a new recurrent breakpoint in the telomeric region was identified distall y to locus D12S158 and to pac 922B22 which is the most telomeric probe avai lable for 12p. Accompanying cryptic deletions were also detected in five pa tients and the commonly deleted region, of around 700 kb, included the ETV6 gene and the D12S391 locus.